1zvq

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(New page: 200px<br /> <applet load="1zvq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zvq, resolution 2.0&Aring;" /> '''Structure of the Q61...)
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<applet load="1zvq" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Structure of the Q61G mutant of Ras in the GDP-bound form'''<br />
'''Structure of the Q61G mutant of Ras in the GDP-bound form'''<br />
==Overview==
==Overview==
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The flexibility of the conserved 57DTAGQ61 motif is essential for Ras, proper cycling in response to growth factors. Here, we increase the, flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal, structure of the RasQ61G mutant reveals a new conformation of switch 2, that bears remarkable structural homology to an intermediate for GTP, hydrolysis revealed by targeted molecular dynamics simulations. The, mutation increased retention of GTP and inhibited Ras binding to the, catalytic site, but not to the distal site of Sos. Most importantly, the, thermodynamics of RafRBD binding to Ras are altered even though the, structure of switch 1 is not affected by the mutation. Our results suggest, that interplay and transmission of structural information between the, switch regions are important factors for Ras function. They propose that, initiation of GTP hydrolysis sets off the separation of the Ras/effector, complex even before the GDP conformation is reached.
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The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1ZVQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZVQ OCA].
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1ZVQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVQ OCA].
==Reference==
==Reference==
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[[Category: gtpase]]
[[Category: gtpase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:42:00 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:37 2008''

Revision as of 14:19, 21 February 2008

Image:1zvq.gif

1zvq, resolution 2.0Å

Drag the structure with the mouse to rotate

Structure of the Q61G mutant of Ras in the GDP-bound form

Contents

Overview

The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached.

Disease

Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]

About this Structure

1ZVQ is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Structure of a transient intermediate for GTP hydrolysis by ras., Ford B, Hornak V, Kleinman H, Nassar N, Structure. 2006 Mar;14(3):427-36. PMID:16531227

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